NICOTINE,
C
10
H
14
N
2
, an alkaloid, found with small quantities of nicotimine,
C
19
H
14
N
2
, nicoteine,
C
10
H
12
N
2
, and nicotelline,
C
10
H
8
N
2
, in tobacco. The name is taken from
Nicotiana
, the tobacco plant, so called after Jean Nicot (1530?1600), French ambassador at Lisbon, who introduced tobacco into France in 1560. These four alkaloids exist in combination in tobacco chiefly as malates and citrates. The alkaloid is obtained from an aqueous extract of tobacco by distillation with slaked lime, the distillate being acidified with oxalic acid, concentrated to a syrup and decomposed by potash. The free base is extracted by ether and fractionated in a current of hydrogen. It is a colourless oil, which boils at 247
° C.
(745
mm.
), and when pure is almost odourless. It has a sharp burning taste, and is very poisonous. It is very hygroscopic, dissolves readily in water, and rapidly undergoes oxidation on exposure to air. The free alkaloid is strongly laevo-rotatory. F. Ratz (
Monats.
, 1905, 26, p. 1241) obtained the value [
a
]
D
=?169·54° at 20°; its salts are dextro-rotatory. It behaves as a di-acid as well as a di-tertiary base.
On oxidation with chromic or nitric acids, or potassium permanganate, it yields nicotinic acid or
β
-pyridine carboxylic acid,
C
5
H
4
N·
CO
2
H
; alkaline potassium ferricyanide gives nicotyrine,
C
10
H
10
N
2
, and hydrogen peroxide oxynicotine,
C
10
H
14
N
2
O
. Oxidation of its isomethylhydroxide with potassium permanganate yields trigonelline,
C
7
H
7
NO
2
(A. Pictet and P. Genequand,
Ber.
, 1897, 30, p. 2117). It gives rise to various decomposition products such as pyridine, picoline, &c., when its vapour is passed through a red-hot tube. The hydrochloride on heating with hydrochloric acid gives methyl chloride (B. Blau,
Ber.
, 1893, 26, p. 631). Hydriodic acid and phosphorus at high temperature give a dihydro-compound, whilst sodium and alcohol give hexa- and octo-hydro derivatives. Nicotine may be recognized by the addition of a drop of 30% formaldehyde, the mixture being allowed to stand for one hour and the solid residue then moistened by a drop of concentrated
sulphruic acid, when an intense rose-red colour is produced (I.
Schindelmeiser,
Pharm. Zentralhalle
, 1899, 40, p. 704).
The constitution of nicotine was established by A. Pinner (see
papers in the
Berichte
, 1891 to 1895). With bromine in acetic acid
solution at ordinary temperature, nicotine yields a perbromide,
C
10
H
10
Br
2
N
2
O?HBr
3
, which with sulphur dioxide, followed by
potash, gives dibromcotinine, C
10
H
10
Br
2
N
2
O, from which cotinine,
C
10
H
12
N
2
O, is obtained by distillation over zinc dust. By heating
nicotine with bromine in hydrobromic acid solution for some hours
at 100° C., dibromticonine hydrobromide, C
10
H
8
N
2
Br
2
O
2
?HBr,
results. Dibromcotinine on hydrolysis yields oxalic acid,
methylamine and
β
-methyl pyridyl ketone: C
10
H
10
Br
2
N
2
O + 3H
2
O + O=
H
2
C
2
O
4
+ CH
3
NH
2
+ C
5
H
4
N?COCH
3
+ 2HBr; whilst dibromticonine
yields methylamine, malonic acid and nicotinic acid: C
10
H
8
Br
2
N
2
O +
4H
2
O=CH
3
NH
2
+ CH
2
(CO
2
H)
2
+ C
5
H
4
N?CO
2
H + 2HBr, or if heated
with zinc and caustic potash, methyl amine and pyridyl-
βγ
-dioxybutyric
acid. Thus the groupings
,??C?C??>N?CH
2
?and??C?C?C?
exist in the molecule, and the alkaloid is to be represented as
α
-pyridyl-N-methyl-pyrollidine.
This result has been confirmed by its synthesis by A. Pictet and
P. Crepieux (
Comptes rendus
, 1903, 137, p. 860) and Pictet and
Rotschy (
Ber.
, 1904, 37, p. 1225):
β
-aminopyridine is converted
into its mucate, which by dry distillation gives N-
β
-pyridylpyrrol.
By passing the vapour of this compound through a red-hot tube,
it yields the isomeric
αβ
-pyridylpyrrol, the potassium salt of which
with methyl iodide gives substance methylated both in the pyridine
and pyrrol nuclei. By distillation over lime, the methyl group is
removed from the pyridine ring, and the resulting
α
-pyridyl-N-methylpyrrol
gives
i
-nicotine on reduction. This base is resolved into
its active components by
d
-tartaric acid,
l
-nicotine-
d
-tartrate
crystallizing out first. The natural (laevo) base is twice as toxic as
the dextro. The following formulae are
important:?
|
|
|
|
|
N-
β
-Pyridylpyrrol,
|
|
αβ
-pyridylpyrrol,
|
|
nicotine.
|
Acetyl and benzoyl derivatives of nicotine on hydrolysis do not
yield nicotine, but an isomeric, inactive oily liquid (metanicotine).
It is a secondary base, and boils at 275°-278° C.
Nicotimine
is a colourless liquid which boils at 250°-255° C. Its
aqueous solution is alkaline.
Nicoteine
is a liquid which boils at
267° C. It is separated from the other alkaloids of the group by
distilling off the nicotine and nicotimine in steam and then fractionating
the residue. It is soluble in water and is very poisonous.
Nicotelline
crystallizes in needles which melt at 147° C. and is readily
soluble in hot water.